Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs

Abstract Recently, research has focused on targeting the oxidative and metabolic vulnerabilities in cancer cells. Natural compounds like curcumin that target such susceptibilities have failed further clinical advancements due to the poor stability and bioavailability as well as the need of high effe...

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Autores principales:	Christopher Pignanelli, Dennis Ma, Megan Noel, Jesse Ropat, Fadi Mansour, Colin Curran, Simon Pupulin, Kristen Larocque, Jianzhang Wu, Guang Liang, Yi Wang, Siyaram Pandey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/541280dca3a14ddc9144ea845137126b
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spelling	oai:doaj.org-article:541280dca3a14ddc9144ea845137126b2021-12-02T15:05:02ZSelective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs10.1038/s41598-017-01230-42045-2322https://doaj.org/article/541280dca3a14ddc9144ea845137126b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01230-4https://doaj.org/toc/2045-2322Abstract Recently, research has focused on targeting the oxidative and metabolic vulnerabilities in cancer cells. Natural compounds like curcumin that target such susceptibilities have failed further clinical advancements due to the poor stability and bioavailability as well as the need of high effective doses. We have synthesized and evaluated the anti-cancer activity of several monocarbonyl analogs of curcumin. Interestingly, two novel analogs (Compound A and I) in comparison to curcumin, have increased chemical stability and have greater anti-cancer activity in a variety of human cancer cells, including triple-negative, inflammatory breast cancer cells. In particular, the generation of reactive oxygen species was selective to cancer cells and occurred upstream of mitochondrial collapse and execution of apoptosis. Furthermore, Compound A in combination with another cancer-selective/pro-oxidant, piperlongumine, caused an enhanced anti-cancer effect. Most importantly, Compound A was well tolerated by mice and was effective in inhibiting the growth of human triple-negative breast cancer and leukemia xenografts in vivo when administered intraperitoneally. Thus, exploiting oxidative vulnerabilities in cancer cells could be a selective and efficacious means to eradicate malignant cells as demonstrated by the curcumin analogs presented in this report with high therapeutic potential.Christopher PignanelliDennis MaMegan NoelJesse RopatFadi MansourColin CurranSimon PupulinKristen LarocqueJianzhang WuGuang LiangYi WangSiyaram PandeyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-25 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher Pignanelli Dennis Ma Megan Noel Jesse Ropat Fadi Mansour Colin Curran Simon Pupulin Kristen Larocque Jianzhang Wu Guang Liang Yi Wang Siyaram Pandey Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs
description	Abstract Recently, research has focused on targeting the oxidative and metabolic vulnerabilities in cancer cells. Natural compounds like curcumin that target such susceptibilities have failed further clinical advancements due to the poor stability and bioavailability as well as the need of high effective doses. We have synthesized and evaluated the anti-cancer activity of several monocarbonyl analogs of curcumin. Interestingly, two novel analogs (Compound A and I) in comparison to curcumin, have increased chemical stability and have greater anti-cancer activity in a variety of human cancer cells, including triple-negative, inflammatory breast cancer cells. In particular, the generation of reactive oxygen species was selective to cancer cells and occurred upstream of mitochondrial collapse and execution of apoptosis. Furthermore, Compound A in combination with another cancer-selective/pro-oxidant, piperlongumine, caused an enhanced anti-cancer effect. Most importantly, Compound A was well tolerated by mice and was effective in inhibiting the growth of human triple-negative breast cancer and leukemia xenografts in vivo when administered intraperitoneally. Thus, exploiting oxidative vulnerabilities in cancer cells could be a selective and efficacious means to eradicate malignant cells as demonstrated by the curcumin analogs presented in this report with high therapeutic potential.
format	article
author	Christopher Pignanelli Dennis Ma Megan Noel Jesse Ropat Fadi Mansour Colin Curran Simon Pupulin Kristen Larocque Jianzhang Wu Guang Liang Yi Wang Siyaram Pandey
author_facet	Christopher Pignanelli Dennis Ma Megan Noel Jesse Ropat Fadi Mansour Colin Curran Simon Pupulin Kristen Larocque Jianzhang Wu Guang Liang Yi Wang Siyaram Pandey
author_sort	Christopher Pignanelli
title	Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs
title_short	Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs
title_full	Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs
title_fullStr	Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs
title_full_unstemmed	Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs
title_sort	selective targeting of cancer cells by oxidative vulnerabilities with novel curcumin analogs
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/541280dca3a14ddc9144ea845137126b
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Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs

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